This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The studies described herein aim to gain a deeper understanding of structure-function relationships in several classes of DNA binding proteins and enzymes. Currently, five projects in the lab have generated crystals requiring synchrotron beamtime: (1) the role of indirect readout by type II restriction endonucleases, (2) the stereochemical cleavage mechanism of DNA cleavage by divalent cation dependent nucleases, (3) the modulation of specificity in a tetrameric type II restriction endonuclease, (4) the recognition of damaged DNA by DNA repair proteins, (5) the recognition code of artificial C2H2 zinc fingers. Many involve the investigation of how proteins and enzymes achieve very high DNA sequence discrimination. The enzymatic mechanisms study the mechanism of DNA cleavage in a model system, which is believed to have much in common with many medically relevant human endonucleases. The DNA repair proteins are important in cellular function in identifying damage for the initiation of the repair process, and also for decision making regarding the cell fate, which can be either repair or programmed cell death. The zinc finger project is in collaboration with the laboratories of Prof. David Segal, UC Davis, and Prof. Carlos Barbas, Scripps Institute, where efforts are under way to create new therapeutics for the identification and treatment of diseases such as cancer and AIDS.